DESCRIPTION: During the initial funding cycle, we conducted a comprehensive investigation of cancer risks in relation to occupational exposures among a cohort of 267,400 Shanghai women textile workers. The cohort had been assembled previously for an intervention trial of the efficacy of breast self-exam. In the initial investigation, we determined cancer incidence (1989-1998), developed a comprehensive job/exposure matrix to reconstruct historical exposures, and conducted a nested case-cohort study to investigate associations of 15 site-specific cancers. The strongest prior hypothesis was that endotoxin, a contaminant of cotton dust, would reduce risk for lung cancer. Consistent with this hypothesis, we observed a very strong inverse dose-response gradient of lung cancer risk with cumulative exposure to endotoxin that was most pronounced for early career exposures (lagged 20 years). Not anticipated were very similar inverse dose-response gradients with endotoxin for cancers of the liver, esophagus, stomach, rectum, pancreas, and breast. We also observed associations of site-specific cancer risks with exposures to other agents, such as silica and cancers of the lung, ovary, and endometrium. In this competing renewal application, we are proposing to extend follow-up of the cohort for an additional 8 years through 2006, thus providing the opportunity to determine the consistency of our initial observations regarding endotoxin, and greatly increasing statistical power to examine other associations (e.g., urinary bladder cancer and dyes). An ongoing study of EMF, shift work, and breast cancer that we are conducting in this cohort will provide quantitative data for those exposures. Data on some relevant non- occupational potential confounders (e.g., spousal smoking history) will supplement currently available covariate data on smoking, alcohol use, and reproductive history. The findings from the proposed study will add considerable new information on the potential anti-carcinogenic effect of endotoxin, and the influences of other occupational exposures on risks for multiple different cancers. Exposures to endotoxin, in particular, and to other agents that are common in the textile industry are widespread in many occupational and environmental settings in the US and throughout the world. As such, the findings from this research have good promise to inform disease prevention strategies, and may also have therapeutic implications. PUBLIC HEALTH RELEVANCE: This competing renewal (R01CA80180) is for an updated study to investigate cancer risks among 267,400 women textile workers in Shanghai. We will investigate dose-response relations for endotoxin and other exposures for cancers of the lung, digestive tract, breast, and reproductive organs.